The molecular sizes of the glucagon receptor and of adenylate cyclase in its ground state and guanine nucleotide- or hormone-activated states have been estimated in hepatic plasma membranes by the use of high energy radiation analysis. The size of the uncoupled, high affinity state of the receptor is in the range of 6.5-8.0 x 10 to the 5th power daltons whereas the size of the receptor when coupled to adenylate cyclase in the presence of GTP ranges from 1.5-2.0 x 10 to the 5th power daltons. The size of adenylate cyclase, in its unactivated state range from 1.2-1.5 x 10 daltons. When activated by GTP or GMP-PNP the enzyme is converted to a smaller size ranging from 2.5-3.0 x 10 to the 5th power daltons. It is concluded that the glucagon receptor and adenylate cyclase exist in the plasma membrane as oligomers, probably tetramers, when the nucleotide regulatory components associated with receptor and enzyme are not occupied by GTP (or GMP-PNP). The guanine nucleotides convert the tetramers to monomers which, in the presence of glucagon, couple within the plen of the plasma membrane to give a high Vmax form of the enzyme, resulting in the generation of cyclic AMP.